The skin, mucous membranes, hair and/or nails constitute a physical barrier between the organism and its environment. The skin is composed of two tissues: the epidermis and the dermis. The adipocytes are found in the deeper layer of the dermis, the hypodermis, and they are organized in lobules, separated by septa of connective tissue that contain vessels, nerves and lymph nodes. The main function of adipocytes is the storage of fat as triglycerides in vacuoles.
Adipose tissue plays a crucial role in the regulation of whole-body fatty acid homeostasis. In periods of caloric abundance it stores free fatty acids (FFAs) in the form of triglycerides through their esterification to glycerol and it releases them back into the circulation in times of energy shortage. Adipose tissue also acts as an endocrine organ capable of secreting cytokines, named as adipokines or adipose tissue-derived proteins.
A deposition of adipose tissue in different parts of the body and a decrease in the muscular mass takes place with the age and the lack of adequate physical activity. Regular exercise brings a decrease in fat accumulation and an increase in muscular endurance, which in turn leads to a firmer aspect of some corporal areas and a better physical appearance. Beneficial effects of exercise are thought to be partly mediated by changes in adipokine profile, that is, by increasing the levels of anti-inflammatory cytokines, such as adiponectin [Golbidi S. and Laher I. “Exercise Induced Adipokine Changes and the Metabolic Syndrome”, J. Diabetes Res., 2014; DOI 2014:726861; Petersen A. M. and Pedersen B. K., “The anti-inflammatory effect of exercise”, J. Appl. Physiol., 2005, 98(4), 1154-1162; LaMonte M. J. et al., “Physical activity and diabetes prevention”, J. Appl. Physiol., 2005, 99, 1205-1213; Bruunsgaard H., “Physical activity and modulation of systemic low-level inflammation”, J. Leukoc. Biol., 2005, 78(4), 819-835]. The effect of the exercise has been described at levels of gene expression, protein ligands, and receptor bindings [Moldoveanu A. I. et al., “The cytokine response to physical activity and training”, Sports Med., 2001, 31(2), 115-144].
Adiponectin (also known as AdipoQ, ACDC, Acrp30, apM-1, APM1, GBP28, ADPN and ADIPQTL1) is a cytokine secreted by adipose tissue during adipocyte differentiation. Human adiponectin consists of 244 amino acids and has a characteristic domain structure with a collagen-like and a globular C1q-like domain, and it circulates in the blood in at least three homomeric complexes, i.e., trimer, hexamer and higher order multimers. Plasma adiponectin level is inversely correlated with body mass index (BMI) and intra-abdominal fat and furthermore, plasma adiponectin level increases by means of aerobic exercise training [Golbidi S. and Laher I. “Exercise Induced Adipokine Changes and the Metabolic Syndrome”, J. Diabetes Res., 2014; DOI 2014:726861].
Adiponectin carries out its function through activation of two kinds of receptors, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). Adiponectin binds to AdipoR1 in skeletal muscle cells, and it activates 5′ AMP-activated protein kinase (AMPK) pathways by phosphorylation, initiating a series of molecular responses which finally leads to the stimulation of glucose uptake, fatty acid oxidation, ATP production and mitochondrial biogenesis [Kadowaki T. and Yamauchi T. “Adiponectin and adiponectin receptors”, Endocr. Rev. 2005, 26:439-451; Golbidi S. and Laher I. “Exercise Induced Adipokine Changes and the Metabolic Syndrome”, J. Diabetes Res., 2014, 2014:726861]. Furthermore, the treatment of human myotubes with adiponectin has been disclosed to induce mitochondrial biogenesis, palmitate oxidation and citrate synthase activity [Civitarese A. E. et al., “Role of adiponectin in human skeletal muscle bioenergetics.” Cell Metab., 2006, 4(1):75-87], therefore, inducing an increase of the strength and tone of the muscle fibers similar to the one achieved by physical exercise.
Skeletal muscles are composed of myocytes that form muscle fibers (myofibers). The myofibers are formed from the fusion of development myoblasts (a type of embryonic progenitor cell) in a process known as myogenesis. There are two major types of muscle fibers which differ in their Myosin heavy chain (MyHC) isoforms and their enzymatic capacity. Muscles are composed by a mixture of different types of muscle fibers. Type I fibers (slow twitch) have aerobic activity, high oxidative capacity due to high mitochondria content (express enzymes that oxidize fatty acids), are myoglobin-rich with red appearance and express the protein marker Myosin heavy chain 7 (MyH7), which is specific for Type I fibers [Couturier A. et al. “Carnitine supplementation to obese Zucker rats prevents obesity-induced type II to type I muscle fiber transition and favors an oxidative phenotype of skeletal muscle” Nutrition & Metabolism, 2013, 10:48]. Type II fibers (fast twitch) have anaerobic activity, low oxidative capacity due to low mitochondria content and depend on glycolytic metabolism to generate ATP (adenosine triphosphate). The proportion of Type I and Type II fibers depends on the action of the muscle: Type I fibers are mainly involved in aerobic exercise, in comparison with Type II fibers, which are mainly involved in anaerobic exercise, i.e. the higher the number of Type I fibers, the higher the muscular endurance. Individuals with high skeletal muscle capillary density and individuals with high proportion of Type I fibers show high concentrations of circulating adiponectin [Ingelsson E. et al., “Associations of Serum Adiponectin with Skeletal Muscle Morphology and Insulin Sensitivity”, J Clin Endocrinol Metab, 2009, 94(3):953-957]. Therefore, an increase in the level of circulating adiponectin is expected to increase the proportion of Type I fibers and the muscular endurance.
Furthermore, adiponectin has been reported to induce or accelerate the healing process of skin wounds [EP1651161 B1] by promoting keratinocyte proliferation and migration [Shibata S. et al. “Adiponectin regulates cutaneous wound healing by promoting keratinocyte proliferation and migration via the ERK signaling pathway”, J. Immunol., 2012, 189(6):3231-41]. Adiponectin has been also reported to increase the collagen synthesis and to upregulate Hyaluronic acid synthase 2 gene expression, which increases the synthesis of hyaluronic acid [Ezure T. et al. “Adiponectin and leptin up-regulate extracellular matrix production by dermal fibroblasts”, Biofactors. 2007, 31(3-4):229-36; Yamane T. et al. “Adiponectin promotes hyaluronan synthesis along with increases in hyaluronan synthase 2 transcripts through an AMP-activated protein kinase/peroxisome proliferator-activated receptor-α-dependent pathway in human dermal fibroblasts”, Biochem. and Biophys. Res. Comm. 2011, 415, 235-238].
Surprisingly the inventors of the present invention have found that the ferment extract from a strain of the Bacillus pumilus species increases the adiponectin levels, mitochondrial activity in muscle, ATP levels in muscle and muscular endurance.